Can Biologics Treat Damaged Cartilage?

Overall response rate was 63%, but complete responses only in 19%

Action Points

Note that this multicenter retrospective study found that anti-TNF biologics may be effective in terms of treating relapsing polychondritis.

Be aware that patients were not treated at random, suggesting that selection effects may play a role in the different outcomes between different biologics.

Some benefits were seen for biologic treatment of relapsing polychondritis, although few patients had complete responses and there was only a modest steroid-sparing effect, a French retrospective study found.

The overall response rate to biologic treatment among 41 patients during the first 6 months of treatment was 63%, whereas the rate of complete response was only 19%, according to Guillaume Moulis, MD, of the University of Toulouse, and colleagues.

And during the first 6 months, the decrease in daily prednisone dose was just 5 mg, with wide variations between patients, the researchers reported online in Annals of the Rheumatic Diseases.

Relapsing polychondritis is a rare inflammatory disorder characterized by cartilage and organ involvement -- most notably affecting the nasal, laryngotracheal, and auricular structures along with the sternal and costal cartilage. A seronegative polyarthritis also may occur, and some patients develop a myelodysplastic syndrome.

The conventional first-line treatment has been corticosteroids, often in high doses, but disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate, azathioprine, and cyclophosphamide also have been used.

The pathogenesis of relapsing polychondritis is incompletely understood, although a role has been postulated for multiple inflammatory cytokines, including tumor necrosis factor (TNF)-α; interleukins 1, 6, and 12; and interferon-γ.

Accordingly, numerous cytokine-targeting biologic agents have been tried in patients with refractory or corticosteroid-dependent disease, but most reports have been single cases or small series with varying endpoints, so efficacy and safety have been difficult to assess.

Therefore, Moulis and colleagues conducted a nationwide study of patients with relapsing polychondritis treated with biologics at 14 centers from 2001 to 2015.

The biologics used included the TNF inhibitors infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel), plus tocilizumab (Actemra), rituximab (Rituxan), anakinra (Kineret), and abatacept (Orencia). All were given in the dosages used for rheumatoid arthritis.

At baseline, patients' mean age was 47, and slightly more than half were women. Auricular chondritis was present in 76% of the patients, nasal chondritis in 83%, and sternal chondritis in 54%. Ocular complications were seen in 44%, vestibular and cochlear manifestations in 37%, and respiratory disease in 59%. Antinuclear antibodies were detected in 54%, anti-collagen II in 20%, and anti-citrullinated protein antibodies in 16%.

Previous medications taken by the patients included methotrexate in 73%, cyclophosphamide in 27%, and azathioprine in 24%. More than 85% of patients were on corticosteroids at the time of biologic initiation, at a mean prednisone-equivalent dosage of 24 mg/day, and almost two-thirds were on concomitant non-biologic DMARDs.

Overall, among the 41 patients there were 105 exposures to biologics, including some re-exposures. This included 60 exposures to TNF inhibitors, 17 to tocilizumab, 15 to anakinra, seven to rituximab, and six to abatacept.

Response rates at 6 months were 71% for rituximab and tocilizumab, 63% for the TNF inhibitors, 53% for anakinra, and 50% for abatacept.

The researchers also looked at response rates at 6 months according to affected organs. For nasal/auricular chondritis, response rates were 100% for rituximab, 78% for tocilizumab, and 75% for abatacept. For joint involvement, TNF inhibitors were the most effective, particularly adalimumab, with a response rate of 50%. For respiratory manifestations, the highest rates were seen for tocilizumab (100%) and the TNF inhibitors (71%).

A total of 21% of biologics were withdrawn because of adverse effects, which most commonly were infections (n=42). Three opportunistic infections occurred, with two being herpes recurrences in patients on anakinra and one zoster with tocilizumab, and one patient who smoked developed lung cancer after 19 months on anakinra.

The researchers also considered whether multiple factors were associated with clinical response at 6 months, but found no significant predictors on a univariate analysis, pointing out that there was a lack of statistical power in the study.

Nonetheless, trends were seen for increased responses among patients on concomitant DMARDs (OR 2.14, 95% CI 0.55-8.38), a history of sternal chondritis (OR 5, 95% CI 1.22-20.45) or sternal chondritis at the time of biologic initiation (OR 3.95, 95% CI 0.90-17.40), and nasal/auricular chondritis at the time of starting a biologic (OR 3.64, 95% CI 0.90-14.61).

The researchers said that as expected, lower response rates were seen among patients with accompanying myelodysplastic syndromes (OR 0.14, 95% CI 0.01-1.51).

"Altogether, this study suggests the need for registries on patients with relapsing polychondritis, in particular to compare biologics with non-biologic DMARDs, which is an important question that was not addressed in this study," Moulis and colleagues wrote. They also called for prospective, head-to-head studies of biologics to more fully examine the efficacy and safety of the individual agents.

Limitations of the study, the team said, included the retrospective design and the possibility of unmeasured factors influencing the choice of biologics.

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